The response rate in patients with metastatic melanoma receiving interleukin-2/lymphokine activated killer cells (IL-2/LAK) is approximately 20%. Tumor-specific monoclonal antibodies can potentiate the antitumor activity of IL-2/LAK in preclinical animal models. Therefore we are initiating a trial adding R24, a murine monoclonal antibody reactive with melanoma tumor cells expressing the ganglioside GD3, to a modified IL-2/LAK regimen. Escalating doses or R24 are administered by 24-hour continuous infusion to cohorts of patients on day 0. The R24 is followed by IL-2 administered as a continuous infusion on days 1-6, followed by a second infusion on days 11-18 given concurrently with LAK cells on days 11, 12, and 14. All patients entering the study have tumor biopsied before treatment, prior to the beginning of LAK infusions, and following the completion of IL-2/LAK. Tumor tissue is tested for R24 binding and antigen saturation, immunophenotyping of tumor infiltrating lymphocytes, expression of tumor-associated antigens and MHC class 1 and 2 molecules, and if possible, expansion and functional characterization of tumor infiltrating lymphocytes. Assays of peripheral blood lymphocytes include phenotyping, measurement of cytotoxicity against melanoma cell lines, and quantitation of proliferation when stimulated with R24. Six patients have been accrued at the first dose level of R24 (3 mg/m2). Accrual will continue until a maximum tolerated dose of R24 in combination with IL-2/LAK is reached.